RT Journal Article
SR Electronic
T1 Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of mouse hematopoietic cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 730358
DO 10.1101/730358
A1 Ross C. Hardison
A1 Yu Zhang
A1 Cheryl A. Keller
A1 Guanjue Xiang
A1 Elisabeth Heuston
A1 Lin An
A1 Jens Lichtenberg
A1 Belinda M. Giardine
A1 David Bodine
A1 Shaun Mahony
A1 Qunhua Li
A1 Feng Yue
A1 Mitchell J. Weiss
A1 Gerd Blobel
A1 James Taylor
A1 Jim Hughes
A1 Doug Higgs
A1 Berthold Gottgens
YR 2019
UL http://biorxiv.org/content/early/2019/08/26/730358.abstract
AB Members of the GATA family of transcription factors play key roles in the differentiation of specific cell lineages by regulating the expression of target genes. Three GATA factors play distinct roles in hematopoietic differentiation. In order to better understand how these GATA factors function to regulate genes throughout the genome, we are studying the epigenomic and transcriptional landscapes of hematopoietic cells in a model-driven, integrative fashion. We have formed the collaborative multi-lab VISION project to conduct ValIdated Systematic IntegratiON of epigenomic data in mouse and human hematopoiesis. The epigenomic data included nuclease accessibility in chromatin, CTCF occupancy, and histone H3 modifications for twenty cell types covering hematopoietic stem cells, multilineage progenitor cells, and mature cells across the blood cell lineages of mouse. The analysis used the Integrative and Discriminative Epigenome Annotation System (IDEAS), which learns all common combinations of features (epigenetic states) simultaneously in two dimensions - along chromosomes and across cell types. The result is a segmentation that effectively paints the regulatory landscape in readily interpretable views, revealing constitutively active or silent loci as well as the loci specifically induced or repressed in each stage and lineage. Nuclease accessible DNA segments in active chromatin states were designated candidate cis-regulatory elements in each cell type, providing one of the most comprehensive registries of candidate hematopoietic regulatory elements to date. Applications of VISION resources are illustrated for regulation of genes encoding GATA1, GATA2, GATA3, and Ikaros. VISION resources are freely available from our website http://usevision.org.